Macrophage activation in murine African trypanosomiasis

Abstract

African trypanosomiasis is accompanied by a profound general immunosuppression in which both suppressive T cells and macrophages (M phi) have been implicated. The present studies define changes in the M phi surface, endocytic and secretory properties, during the infection of mice by Trypanosoma brucei. Peritoneal M phi obtained after the control of the first wave of parasitemia displayed characteristics similar to those activated by intracellular pathogens, such as Mycobacterium bovis bacillus Calmette-Guérin, e.g., the enhanced expression of Ia antigen, decreased M phi-specific antigens, receptors mediating the pinocytosis of mannose-terminal glycoproteins, and an increased ability to secrete plasminogen activator, superoxide anion, and H2O2. Some markers of macrophage activation persisted during the subpatent period before the recurrence of parasitemia, whereas others reverted to normal. Mature T cell function appears not to be essential for M phi activation by T. brucei since the infection of athymic nude mice also induced Ia antigens and plasminogen activator. These studies show that M phi activated by different pathways express common features which may contribute to immune dysfunction observed in trypanosomiasis, as well as in other infections.

Natural Immunity: A T‐Cell‐Independent Pathway of Macrophage Activation, Defined in the scid Mouse

“…Together, these experiments identify IFN-y as a seminal cytokine in the T cell-independent process of macrophage activation in response to microbial challenge; scid mice produce IFN-y in response to bacteria and utilize this cytokine for macrophage activation. The processes described here may also explain other reports of macrophage activation in the absence of T-cell function (Newborg & North 1980, Behbehani et al 1985, Grossinsky et al 1983. Wentworth & Ziegler 1987.…”

Tumour necrosis factor production by monocytes from cattle infected with Trypanosoma (Duttonella) vivax and Trypanosoma (Nannomonas) congolense: possible association with severity of anaemia associated with the disease

“…In endotoxin treatment and bacterial infections, cachexia has been attributed to suppression of lipoprotein lipase by TNF (Beutler & Cerami 1986) and experimental trypanosomiasis in rabbits is associated with deficient lipase activity (Rouzer & Cerami 1980). Second, functional studies have shown that monocytes and macrophages, the main source of TNF, are activated during both experimental murine trypanosomiasis (Grosskinsky et al 1983) and bovine trypanosomiasis (Flynn & Sileghem 1991). Furthermore, this activation is associated with increased cytokine production in murine (Silghem et al 1989) and bovine trypanosomiasis (Sileghem et al 1993).…”

Macrophage procoagulant activity in experimental African trypanosomiasis

“…During infection of mice with T. brucei there is an enhanced expression of macrophage Ia antigens with a concomitant decrease in the mannose receptors (Grosskinsky et al 1983). It has been shown that expression of PCA is dependent on Ia+ macrophages (Geczy et al 1983) and we have demonstrated that induction of secretion of lysosomal enzymes by zymosan is mediated by mannose receptors (Bodmer & Dean 1983).…”

“…We focused our attention on the possible role of macrophages as the causative agents of the coagulation disorder as they have the capacity to synthesize high levels of thromboplastin and other coagulation factors when activated by a variety of agents (reviewed by Dean, Leoni & Rossi 1984) and in conditions where DIC occurs (Semeraro et al 1981,IZIsterud & Flaegstad 1983. Furthermore, previous studies have demonstrated that macrophages are activated during experimental African trypanosomiasis (Grosskinsky et al 1983).…”

“…in vivo after taking up opsonized parasites (Grosskinsky & Askonas 1981), showed several signs of activation (Grosskinsky et al 1983), secreted increased amounts of immunoregulatory factors (Fierer, Salmon & Askonas 1984, Bancroft 1983, and had impaired ability to present listerial antigen to sensitized T-lymphocytes (Bagasra, Schell& Le Frock 1981). However, the mechanism which triggers and controls macrophage activation during this disease is still unknown.…”